A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome
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Renal transplantationBiopsiesRejectionTranscriptomicsMicroarraysBorderline changesInterstitial fibrosis and tubular atrophy
Chamoun, B., Caraben, A., Torres, I. B., Sellares, J., Jiménez, R., Toapanta, N., ... & O’Valle, F. (2020). A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome. International journal of molecular sciences, 21(21), 8237. [doi:10.3390/ijms21218237]
SponsorshipRed de Investigacion Renal REDinREN RD16/0009/0030; Instituto de Salud Carlos III PI 18/01704 PI 18/01382; Sociedad Espanola de Trasplante; Vall d'Hebron Institute of Research (VHIR) grant
Rejection-associated gene expression has been characterized in renal allograft biopsies for cause. The aim is to evaluate rejection gene expression in subclinical rejection and in biopsies with borderline changes or interstitial fibrosis and tubular atrophy (IFTA).We included 96 biopsies. Most di erentially expressed genes between normal surveillance biopsies (n = 17) and clinical rejection (n = 12) were obtained. A rejection-associated gene (RAG) score was defined as its geometric mean. The following groups were considered: (a) subclinical rejection (REJ-S, n = 6); (b) borderline changes in biopsies for cause (BL-C, n = 13); (c) borderline changes in surveillance biopsies (BL-S, n = 12); (d) IFTA in biopsies for cause (IFTA-C, n = 20); and (e) IFTA in surveillance biopsies (IFTA-S, n = 16). The outcome variable was death-censored graft loss or glomerular filtration rate decline 30 % at 2 years. A RAG score containing 109 genes derived from normal and clinical rejection (area under the curve, AUC = 1) was employed to classify the study groups. A positive RAG score was observed in 83% REJ-S, 38% BL-C, 17% BL-S, 25% IFTA-C, and 5% IFTA-S. A positive RAG score was an independent predictor of graft outcome from histological diagnosis (hazard ratio: 3.5 and 95% confidence interval: 1.1–10.9; p = 0.031). A positive RAG score predicts graft outcome in surveillance and for cause biopsies with a less severe phenotype than clinical rejection.